5-62352567-ATTT-ATTTT

Position:

• chr5-62352567-ATTT-ATTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001098511.3(KIF2A):​c.335-9dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,058,038 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: KIF2A NM_001098511.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.330

Genes affected

KIF2A (HGNC:6318): (kinesin family member 2A) The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000288643 (HGNC:):

DIMT1 (HGNC:30217): (DIM1 rRNA methyltransferase and ribosome maturation factor) The protein encoded by this gene is a methyltransferase that is responsible for dimethylation of adjacent adenosines near the 18S rRNA decoding site. The encoded protein is essential for ribosome biogenesis, although its catalytic activity is not involved in the process. The yeast ortholog of this protein functions in the cytoplasm while this protein functions in the nucleus. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-62352567-A-AT is Benign according to our data. Variant chr5-62352567-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 445895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0177 (16106/909874) while in subpopulation SAS AF= 0.0251 (1242/49510). AF 95% confidence interval is 0.0239. There are 1 homozygotes in gnomad4_exome. There are 7998 alleles in male gnomad4_exome subpopulation. Median coverage is 17. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.335-9dupT		splice_region_variant, intron_variant		ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.335-9dupT		splice_region_variant, intron_variant			NP_004511.2
KIF2A	NM_001243953.2	c.335-9dupT		splice_region_variant, intron_variant			NP_001230882.1
KIF2A	NM_001243952.2	c.254-9dupT		splice_region_variant, intron_variant			NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8	c.335-9dupT		splice_region_variant, intron_variant		1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.64+46043dupT		intron_variant		3		ENSP00000502199.1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 70 AN: 148094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000338

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000730

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000570

Gnomad OTH AF: 0.000494

GnomAD4 exome AF: 0.0177 AC: 16106 AN: 909874 Hom.: 1 Cov.: 17 AF XY: 0.0178 AC XY: 7998 AN XY: 449278

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.0251

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome AF: 0.000472 AC: 70 AN: 148164 Hom.: 0 Cov.: 32 AF XY: 0.000555 AC XY: 40 AN XY: 72114

Gnomad4 AFR AF: 0.000369

Gnomad4 AMR AF: 0.000337

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.000730

Gnomad4 NFE AF: 0.000570

Gnomad4 OTH AF: 0.000490

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Oct 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs762620321; hg19: chr5-61648394;